OVERVIEW: What every clinician needs to know

Pathogen name and classification

Chlamydia psittaci — an obligate intracellular bacterium

What is the best treatment?

Treatment is with tetracycline or doxycycline for 10-21 days. Response to treatment is usually prompt. Some patients have severe fatigue that persists for 2-3 months following resolution of the acute illness. A longer course of treatment has been recommended to prevent relapse. Erythromycin is an alternative to treatment with a tetracycline but may be less efficacious in severe cases. There is less than a 1% mortality rate in treated cases.

Respiratory quinolones, such as moxifloxacin, gatifloxacin, and levofloxacin, are also effective. Based on susceptibility testing, ciprofloxacin will likely be effective as well.

One of the difficulties in interpreting data on antibiotic susceptibility of C. psittaci is the lack of standardized methodology. With macrolides, the minimal inhibitory concentration varies, depending on the cell line used. The minimal inhibitory concentration (MIC) is also influenced by the time at which the antimicrobial is added after infection.

An ovine strain of C. psittaci was tested for susceptibility to 30 antibiotics. The activity of the antibiotics fell into 4 groups:

Azithromycin, clarithromycin, and erythromycin all show good activity against C. psittaci with MICs of 0.125, 0.25, and 0.5 mg/L, respectively. High level resistance to azithromycin due to a point mutation in 23S rRNA gene does occur spontaneously.

A number of fluoroquinolones have very good activity in vitro against C.psittaci. Ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin have MICs of 2, 0.5, 0.125, and 0.125 mg/L, respectively.

How do patients contract this infection, and how do I prevent spread to other patients?

Epidemiology

C.psittaci is transmitted to man by direct contact with infected birds or by inhalation of aerosolized organisms in dried feces or respiratory secretions from infected birds.

A history of exposure to birds is a clinical tip to the diagnosis of psittacosis; however, psittacosis can occur in the absence of such exposure, as illustrated by an outbreak of psittacosis in the Blue Mountains in New South Wales, Australia. In this study, additional risk factors for the spread of psittacosis became evident. Fifty-nine persons were infected, and, in a case control study, the risk factors were 50-64 years of age, direct contact with wild birds, and mowing lawns without a grass catcher. The latter activity probably aerosolized organisms from bird droppings on the lawn.

Psittacosis is uncommon in children. Adults 35-55 years of age seem to be primarily affected.

In an outbreak in a veterinary teaching hospital, 10/29 (34%) individuals who were exposed were infected. One person presented with sepsis syndrome requiring admission to an intensive care unit for multi-organ failure; two people had pneumonia; and the remaining seven were asymptomatic or had a mild illness managed in an ambulatory setting.

An outbreak of psittacosis among a mixed poultry flock in Germany led to infection on 100 small poultry farms. Twenty-four people reported to their physicians with a flu-like illness. All had psittacosis. Seven required hospitalization, three of whom were ill enough to require intensive care.

Up to 30% of households that have purchased infected birds develop psittacosis.

Eighteen people developed psittacosis following a visit to a bird show in Nijmegen, Netherlands.

In a study of community acquired pneumonia requiring admission to 15 teaching hospitals in Canada, 2/272 (0.77%) had pneumonia due to a feline strain of C. psittaci.

Human to human transmission does occur but it is uncommon.

Since 1996, fewer than 50 cases of psittacosis are reported each year in the United States. Indeed, during 2006-10, there were 21, 12, 8, 9, and 4 cases, respectively.

Infection control issues

Person to person transmission has been suggested but not proven. Standard infection control precautions are sufficient and isolation is not required.

The Center for Disease Control and Prevention (CDC) has the following recommendations for prevention of transmission of C. psittaci to persons and birds:

Persons at risk should know about the risk(s) and wear protective clothing, gloves, and an N95 respirator for contact with infected birds or when cleaning cages. If potentially infected birds are to undergo necropsy, the carcass should be wet with detergent and water to prevent aerosolization, and the procedure should be carried out in a biological safety cabinet.

Maintain accurate records of all bird-related transactions to aid in identifying sources of infected birds and potentially exposed persons.

Avoid purchasing or selling birds that have signs of Avian Chlamydiosis. Signs include ocular or nasal discharge, diarrhea, or low body weight.

Isolate newly acquired birds, including those that have been to shows, exhibitions, fairs, and other events, for 30-45 days and test or prophylactically treat them before adding them or returning them to a group.

Test birds before they are boarded or sold on consignment. House them in a room separate from other birds.

Practice preventive husbandry. Position cages to prevent the transfer of fecal matter, feathers, food, and other materials from one cage to another. Do not stack cages and be sure to use solid-sided cages or barriers if cages are adjoining. The bottom of the cage should be made of a wire mesh. Litter that will not produce dust (e.g., newspapers) should be placed underneath the mesh. Clean all cages, food bowls, and water bowls daily. Soiled bowls should be emptied, cleaned with soap and water, rinsed, placed in a disinfectant solution, and rinsed again before reuse. Between occupancies by different birds, cages should be thoroughly scrubbed with soap and water, disinfected, and rinsed in clean, running water. Exhaust ventilation should be sufficient to prevent accumulation of aerosols.

Prevent the spread of infection. Isolate birds requiring treatment. Rooms and cages where infected birds were housed should be cleaned immediately and disinfected thoroughly. When the cage is being cleaned, transfer the bird to a clean cage. Thoroughly scrub the soiled cage with a detergent to remove all fecal debris, rinse the cage, disinfect it (allowing at least 5 minutes of contact with the disinfectant), and re-rinse the cage to remove the disinfectant. Discard all items that cannot be adequately disinfected (e.g., wooden perches, ropes, nest material, and litter). Minimize the circulation of feathers and dust by wet-mopping the floor frequently with disinfectants and preventing air currents and drafts within the area. Reduce contamination from dust by spraying the floor with a disinfectant or water before sweeping it. Do not use a vacuum cleaner, as it can aerosolize infectious particles. Frequently remove waste material from the cage (after moistening the material) and burn or double-bag the waste for disposal. Care for healthy birds before handling isolated or sick birds.

Use disinfection measures. C. psittaci is susceptible to most disinfectants and detergents, as well as heat; however, it is resistant to acid and alkali. A 1:1000 dilution of quaternary ammonium compounds (e.g., Roccal® or Zephiran®) is effective, as is 70% isopropyl alcohol, 1% Lysol®, 1:100 dilution of household bleach (i.e., 2.5 tablespoons per gallon), or chlorophenols. Many disinfectants are respiratory irritants and should be used in a well-ventilated area. Avoid mixing disinfectants with any other product.

Currently there are no vaccines that will protect against C. psittaci.

What host factors protect against this infection?

In humans, following inhalation, C. psittaci spreads via the bloodstream, eventually reaching the alveoli and the reticuloendothelial cells of the liver and spleen. A lymphocytic inflammatory response occurs in the alveoli and interstitium of the lungs. This results in thickening edema of the alveolar walls and interstitial tissues. Occasionally, necrosis occurs. Histologically, the alveolar spaces are filled with fluid, red blood cells, and lymphocytes. The macrophages may contain Levinthal-Coles-Lille. These cytoplasmic inclusions are characteristic of psittacosis.

In turkeys, C. psittaci infects epithelial cells and macrophages in the respiratory tract. This is followed by spread via the blood stream and localization of the organisms in epithelial cells and macrophages in various organs.

What are the clinical manifestations of infection with this organism?

Clinical Features

In birds, psittacosis manifests as anorexia, apathy, ocular and nasal discharge, diarrhea, and conjunctivitis. The organism is present in high concentrations in the droppings of birds. A carrier state can occur, and then there is intermittent shedding. Crowding and transport result in increased spread of the infection among a bird colony.

In humans, the clinical spectrum of C. psittaci infection is wide, ranging from a subclinical illness to severe pneumonia.The incubation period is 5-15 days. Fever, rigors, sweats, and headache are common. Cough occurs in 50-100% of patients, but it usually appears late in the course of illness and usually is nonproductive or productive of mucoid sputum. Rarely, there is hemoptysis. About 20% of patients have no respiratory symptoms. A typhoidal form (remember Ritter’s original description of pneumo-typhus) presents with fever, bradycardia, and malaise. One author described five modes of presentation:

fever with rigors, sweats, and constitutional symptoms but no localizing features, occurring in 41% of the patients

prominent cough and occasional dyspnea in association with fever in 33%

severe headaches suggestive of meningitis

diarrhea, which occurred in two patients

pharyngitis, which occurred in 21% of patients

An alteration of mental status was noted in 12%. A sixth presentation, that of a mononucleosis-like syndrome, could be added. In this presentation, patients have fever, pharyngitis, hepatosplenomegaly, and lymphadenopathy.

Psittacosis during pregnancy is uncommon, but when it occurs it may be severe. An outbreak of sheep-associated psittacosis in the Faroe Islands in 1938 resulted in infection of 14 pregnant women, 11 of whom died. Two cases of psittacosis during pregnancy have been reported from the United States, and in this review 11 other case were identified. Thus, the experience with psittacosis during pregnancy is limited. However, it seems that it manifests as a flu-like illness. Thrombocytopenia and or coagulopathy occurred in 85% of the 13 patients. Hepatic and pulmonary manifestations occur in most patients. Eleven of 14 pregnancies ended in fetal death, and 13 of the 14 mothers recovered. It is recommended that pregnant women avoid contact with psittacine birds and with the birth products of goats and sheep.

Chronic follicular conjunctivitis is another manifestation of psittacosis. These patients have an enlarged preauricular lymphnode and punctate epithelial keratitis. It has been seen in bird fanciers and laboratory workers.

The white blood cell count is usually normal in psittacosis. Eosinophilia may occur during convalescence. Macfarlane and colleagues compared the radiographic features of 10 patients with C. psittaci pneumonia, 49 with Legionnaire’s disease, 91 with pneumococcal pneumonia, and 46 with Mycoplasma pneumoniae pneumonia. No distinctive pattern was seen for any group. Forty percent of the psittacosis patients had multilobe involvement, and 20% had a pleural effusion. In this series, none of the patients with psittacosis showed radiographic deterioration following admission, as compared with 65% of the patients with Legionnaire’s disease, 52% of those with bacteremic pneumococcal pneumonia, and 25% with mycoplasma pneumonia. Fifty percent of the patients with psittacosis pneumonia showed clearing of the pneumonic opacities by 4 weeks; however, 30% were still unresolved by 12 weeks. In a review of 43 cases of psittacosis, Coutts and colleagues found that 12 (28%) had a normal chest radiograph. Segmental consolidation was most frequent (31%); 21% had lobar consolidation, and 19% had multilobar involvement.

The pleural fluid in psittacosis may have a high adenosine deaminase level. This could result in confusion with tuberculosis, since an adenosine deaminase level of greater than 43 IU/L in pleural fluid is believed to be sensitive and specific for tuberculosis.

Two fatal cases of psittacosis were reported from Budapest. A 69 year-old female poultry worker was admitted following a 5 day illness. There was extensive pneumonia involving the left lung and the right lower lobe. She was admitted to ICU but died later the same day from a massive pulmonary embolus. A post mortem, there was extensive bronchopneumonia in the left lung and small disseminated foci of infection the right lower lobe. The second patient, a 48 year-old woman, also a poultry worker, was admitted with a 2-week history of fever and non-productive cough. She had extensive involvement of the right lung and the left lower lobe by pneumonia radiographically. Over the next 2 days, she deteriorated and required admission to ICU for respiratory failure. On day 3 in ICU (hospital day 5), she died from multiorgan failure. Post mortem showed confluent pneumonia, septic spleen and kidneys, and an alcoholic fatty liver. The first patient died from a pulmonary embolism, but the second patient had fulminant psittacosis. Although fatal cases of psittacosis are rare, it does look as if respiratory failure due to psittacosis is an ominous prognostic sign. Severe respiratory insufficiency due to psittacosis is uncommon, with only 12 reported cases from 1963 to 1993. Ten of these had a history of exposure to birds. Seven had neurologic manifestations, six had gastrointestinal symptoms, and four were in acute renal failure requiring hemodialysis. Eight patients (67%) died, three within 48 hours of admission.

Chlamydia psittaci and MALT (mucosa associated lymphoid tissue type) lymphomas are extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue. They are the second most common indolent lymphomas among all non-Hodgkin lymphomas originating from the B-cells of the marginal zone of MALT. There is a considerable amount of evidence that lymphomageneis of the marginal zone is associated with chronic antigenic stimulation by microbial pathogens or autoantigens. The best example is the association of Helicobacter pylori with gastric lymphoma.

What common complications are associated with infection with this pathogen?

A variety of complications can occur, including acrocyanosis, superficial venous thrombosis, and splinter hemorrhages. Panniculitis, erythema multiforme, and erythema nodosum are other cutaneous manifestations. Encephalitis, meningitis, cerebellar involvement, cranial nerve palsies, intracranial hypertension, and transverse myelitis are central nervous system manifestations. Acute renal failure, interstitial nephritis, pancreatitis, and thrombocytopenic purpura have also complicated psittacosis. Other complications include reactive arthritis and hemophagocytosis.A post infectious fatigue syndrome also occurs, but there are very little data on the frequency of this complication. Respiratory failure, especially when psittacosis occurs during pregnancy, is also a complication.

How should I identify the organism?

· Parasite Life Cycle

C. pisttaci along with other chlamydiae has a unique development cycle with elementary (the infectious particle) and reticulate(the intracellular replicative particle) bodies. After infection, elementary bodies (about 350 nm in diameter) attach to the host cell by electrostatic binding and enter the cell by endocytosis. Elementary bodies (EB) differentiate into reticulate bodies (about 850 nm in diameter), which undergo binary fission. After about 36 hours, the reticulate bodies (RBs) differentiate back into EBs. A large number of EBs accumulate in the cell (around 500-1000), yet host cell function is not affected. These large accumulations, or microcolonies, are referred to as intracytoplasmic inclusions. During this process, chlamydial antigens are released onto the host cell surface, inducing a host immune response. Release of EBs occurs by several processes, including extrusion of the inclusion. The elementary body is metabolically inactive, whereas the reticulate body is metabolically active.

In 1930, Lewinthal, Coles, Lille described small filterable bodies in infectious material. Inclusion bodies in the cytoplasm of macrophages from birds or humans infected with C. psittaci are now known as Lewinthal-Coles-Lille bodies. These bodies stain well with Wright's Giemsa.

Chlamydiae are organisms that are easily damaged. To maximize the chance of isolating such organisms, the specimens should be placed in transport media, kept cold, and transported to the laboratory as soon as possible. Sputum, bronchial washings, biopsy specimens, and blood are suitable specimens from which to isolate C. psittaci. This organism is quite infectious and has caused many laboratory-acquired infections. It should only be handled in a Biocontainment Level 3 Laboratory. Specimens are inoculated onto cyclohexamide-treated monolayers of McCoy cells in shell vials. Following incubation for 48-72 hours, organisms are detected by staining with group specific fluorescent monoclonal antibodies.

· Serology

A four-fold increase in antibody titer between acute and convalescent serum samples is the most common method of diagnosis. The complement fixation test or the microimmunofluoresence (MIF) tests can be used. A single IgM titer greater than or equal to 1:32 by MIF is also diagnostic. The MIF test has improved the sensitivity and specificity of testing for C. psittaci. However, cross reactivity between C. pneumoniae and C. psittaci can be a problem. Cross reactivity with Legionella longbeacheae has also been reported.

In a study of 78 patients in whom a diagnosis of psittacosis was made on the basis of appropriate clinical symptoms following exposure to sick birds, the complement fixation test identified 36 of 78 (46%) as positive, while the MIF test identified 48 of 78 (61%). The investigators used eight strains of C. psittaci in the MIF test. Others have noted that the MIF test can be falsely negative. Thus, more than one strain of C. psittaci should be used in the MIF test. Four serologic reaction patterns were observed among their 78 patients: (1) positive CF and MIF tests (46%), (2) anticomplementary or negative CF test and positive MIF test (15%), (3) positive serologic response to C. pneumoniae (9%), and (4) negative antibody titer using both CF and MIF tests (29%).

PCR has been used to amplify C. psittaci from a variety of specimens. Primers using the OmpA and the inclusion membrane protein A genes have been used.

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